GRADE-ADOLOPMENT of hyperthyroidism treatment guidelines for a Pakistani context.

INTRODUCTION: The prevalence of hyperthyroidism in Pakistan is 2.9%, which is two times higher than in the United States. Most high-quality hyperthyroidism clinical practice guidelines (CPGs) used internationally originate from high-income countries in the West. Local CPGs in Pakistan are not backed by transparent methodologies. We aimed to produce comprehensive, high-quality CPGs for the management of hyperthyroidism in Pakistan. METHODS: We employed the GRADE-ADOLOPMENT approach utilizing the 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis as the source CPG. Recommendations from the source guideline were either adopted as is, excluded, or adapted according to our local context. RESULTS: The source guideline included a total of 124 recommendations, out of which 71 were adopted and 49 were excluded. 4 recommendations were carried forward for adaptation via the ETD process, with modifications being made to 2 of these. The first addressed the need for liver function tests (LFTs) amongst patients experiencing symptoms of hepatotoxicity while being treated with anti-thyroid drugs (ATDs). The second pertained to thyroid status testing post-treatment by radioactive iodine (RAI) therapy for Graves' Disease (GD). Both adaptations centered around the judicious use of laboratory investigations to reduce costs of hyperthyroidism management. CONCLUSION: Our newly developed hyperthyroidism CPGs for Pakistan contain two context-specific modifications that prioritize patients' finances during the course of hyperthyroidism management and to limit the overuse of laboratory testing in a resource-constrained setting. Future research must investigate the cost-effectiveness and risk-benefit ratio of these modified recommendations.

Axial muscle involvement in patients with limb girdle muscular dystrophy type R9.

INTRODUCTION/AIMS: Limb girdle muscular dystrophy type R9 (LGMDR9) is characterized by progressive weakness of the shoulder and hip girdles. Involvement of proximal extremity muscles is well-described whereas information about axial muscle involvement is lacking. It is important to recognize the involvement of axial muscles to understand functional challenges for the patients. The aim of this study was to investigate the involvement of axial and leg muscles in patients with LGMDR9. METHODS: This observational, cross-sectional study investigated fat replacement of axial and leg muscles in 14 patients with LGMDR9 and 13 matched, healthy controls using quantitative MRI (Dixon technique). We investigated paraspinal muscles at three levels, psoas major at the lumbar level, and leg muscles in the thigh and calf. Trunk strength was assessed with stationary dynamometry and manual muscle tests. RESULTS: Patients with LGMDR9 had significantly increased fat replacement of all investigated axial muscles compared with healthy controls (P < .05). Trunk extension and flexion strength were significantly reduced in patients. Extension strength correlated negatively with mean fat fraction of paraspinal muscles. Fat fractions of all investigated leg muscles were significantly increased versus controls, with the posterior thigh muscles being the most severely affected. DISCUSSION: Patients with LGMDR9 have severe involvement of their axial muscles and correspondingly have reduced trunk extension and flexion strength. Our findings define the axial muscles as some of the most severely involved muscle groups in LGMDR9, which should be considered in the clinical management of the disorder and monitoring of disease progression.

Favourable prognosis in metastatic adrenal carcinoma: An unexpected outcome.

The case of a 45-year-old male patient diagnosed with European Network for the Study of Adrenal Tumours (ENSAT) criteria, stage IV adrenocortical carcinoma (ACC) with unexpectedly prolonged survival is being reported. The patient underwent resection of stage IV ACC and despite suboptimal adherence to postoperative mitotane and chemotherapy, had a prolonged survival spanning almost seven years. The possible reasons for such an outcome are discussed. ACC is a rare tumour with stage 4 disease known to be associated with a particularly grim prognosis. A low grade on histology (mitotic index 11-12 per 50 HPF) was likely responsible for the prolonged survival of our patient. Low grade disease may predict extended survival in stage IV ACC.

Muscle involvement assessed by quantitative magnetic resonance imaging in patients with anoctamin 5 deficiency.

OBJECTIVE: Using magnetic resonance imaging (MRI) and stationary dynamometry, the aim was to investigate the muscle affection in paraspinal muscles and lower extremities and compare the muscle affection in men and women with anoctamin 5 (ANO5) deficiency. METHODS: Seventeen patients (seven women) with pathogenic ANO5-mutations were included. Quantitative muscle fat fraction of back and leg muscles were assessed by Dixon MRI. Muscle strength was assessed by stationary dynamometer. Results were compared with 11 matched, healthy controls. RESULTS: Muscle involvement pattern in men with ANO5-deficiency is characterized by a severe fat replacement of hamstrings, adductor and gastrocnemius muscles, while paraspinal muscles are only mildly affected, while preserved gracilis and sartorius muscles were hypertrophied. Women with ANO5-myopathy, of the same age as male patients, were very mildly affected, showing muscle affection and strength resembling that found in healthy persons, with the exception of the gluteus minimus and medius and gastrocnemii muscles that were significantly replaced by fat. Although individual muscles showed clear asymmetric involvement in a few muscle groups, the overall muscle involvement was symmetric. CONCLUSIONS: Patients with ANO5-deficiency have relatively preserved paraspinal muscles on imaging and only mild reduction of trunk extension strength in men only. Our study quantifies the large difference in muscle affection in lower extremity between women and men with ANO5-deficiency. The clinical notion is that affection may be very asymmetric in ANO5-deficiency, but the present study shows that while this may be true for a few muscles, the general impression is that muscle affection is very symmetric.

Association of thyroid antibodies status on the outcomes of pregnant women with hypothyroidism (maternal hypothyroidism on pregnancy outcomes, MHPO-4).

BACKGROUND: Autoimmunity increases with age and is often commonly evaluated in women of the reproductive age group. Prevalence of thyroid antibodies is common even in euthyroid pregnant women. We aim to compare the association of thyroid antibody status on the maternal and neonatal outcomes in pregnant women with hypothyroidism. METHODS: We conducted a cross-sectional retrospective study on 718 cases in the Aga Khan University Hospital. Information was collected on pregnant women who have been diagnosed with hypothyroidism before conception or during their antenatal period. Laboratory data were recorded for thyroid peroxidase antibodies, anti-thyroglobulin antibodies, and thyroid-stimulating hormone levels. Maternal and neonatal outcomes were also noted from medical file records. Data analysis was performed on Statistical Package for the Social Sciences version 20.0. RESULTS: Overall, 146 out 718 cases were included for final analysis. Thyroid peroxidase antibodies were positive in 66.4% and anti-thyroglobulin was positive in 52.1% cases, whereas 43.8% of cases had both antibodies positive. Pre-gestational diabetes was significantly associated with thyroid autoimmunity. There was a 73% less chance of gestational hypertension for thyroid autoimmune groups. Gestational diabetes and maternal (chronic) hypertension were found to have an independent effect on postpartum hemorrhage. Hypertensive disorders in pregnancy were found to have an independent risk for premature birth. CONCLUSION: Our study reports a 74.7% prevalence of positive thyroid antibodies in hypothyroid pregnant women, with higher association with pre-gestational diabetes. Gestational hypertension was least likely to occur in thyroid autoimmune groups. None of the outcomes were independently associated with worse outcomes.

Clinical outcomes of Sodium-glucose cotransporter-2 inhibitors in patients with Type 2 Diabetes Mellitus: An observational study from Pakistan.

OBJECTIVE: To determine the efficacy and safety of Sodium-glucose cotransporter-2 inhibitors (SGLT2i) use in the Pakistani population. METHODS: Retrospective review of initial 100 patients who were prescribed with any agent of the SGLT2i group from July 1, 2018, to January 2019 at Aga Khan University Hospital, Karachi. SGLT2i was offered to patients of above 18 years of age with inadequate glycemic control on existing antidiabetic agents. Changes in HbA1c, the Body Mass Index (BMI), serum creatinine, any decrease in the requirement of insulin and sulphonylurea dose along with any side effects reported by the patients on follow-up visits. RESULTS: Most study participants were females (56%) with the mean age of 52±10 years. Substantial changes were observed in the HbA1c (7.5±1.1%, 7.9±1.2% from 8.7±1.5%, p < 0.01), BMI (31.4±5.8, 31.8±5.8 from 32.4±5.9kg/m2, p < 0.01) and in creatinine (0.71±0.1, 0.75±0.1 from 0.79±0.1 mg/dl, p < 0.01) at three and six months of follow up visits. The reduction in insulin and sulphonylurea doses was also significant. Adverse drug events that led to drug discontinuation in 14 individuals were, Urinary tract infection (UTI) (seven patients), Genital infection (three patients), nausea +UTI, abdominal pain +UTI, mild Diabetic Ketoacidosis, and polyuria (one patient each). None reported Fournier's gangrene, limb amputation, or fracture. CONCLUSION: SGLT2i significantly improved glycemic control, BMI, and serum creatinine in the Pakistani population with a very low number of observed adverse events.

Altered sperm parameters and subclinical hypothyroidism; A cross sectional study in Karachi, Pakistan.

OBJECTIVE: The purpose of this study is to compare the thyroid hormone (TH) profile in male infertile subjects with normal and altered sperm parameters and assess its relationship with spermogram and reproductive hormones. DESIGN: This cross-sectional study was conducted in Karachi from August 2017 till September 2018 on 376 male subjects between 25 and 55 years of age. The reference values for the "Normal Sperm Parameters" group was; sperm count (TC) >39 million per ejaculate, total sperm motility (Progressive and Non-progressive) >40% and normal morphology of ≥4%. Male subjects, having any one of the sperm parameters below the reference values comprised the group of "Altered Sperm Parameters". The thyroid profile; Thyroxine (T4), triiodothyronine (T3), thyroid stimulating hormone, Thyroid Peroxidase antibodies (Anti-TPO) was estimated in addition to reproductive hormones Testosterone and Sex hormone binding globulin (SHBG). Independent sample T test and Analysis of Variance was applied for comparison of groups. Linear regression was performed and unadjusted and adjusted beta coefficient with 95% CI was reported. A P-value of <.05 was considered significant. RESULTS: Two hundred and sixteen subjects had normal, whereas 160 had "Abnormal Sperm Parameters." In "Normal Sperm Parameter" group; 206 (95.3%) were euthyroid while 10 (4.6%) were having subclinical hypothyroidism (SCH). Among the "Abnormal Sperm Parameters" group; eighty-seven (54%) subjects were euthyroid, sixty-two (38.75%) had SCH and eleven (6.8%) were having overt hypothyroidism. Testosterone and SHBG were significantly lower in "Altered Sperm Parameters" group as compared with "Normal Sperm Parameters" (P < .001 for both). CONCLUSION: A higher frequency of SCH, decreased levels of testosterone and SHBG was observed in the "Altered Sperm Parameters" group. The results establish relationship of disturbance in TH with alteration of sperm parameters and reproductive hormones thus contributing to male infertility.

Non Invasive Follicular Thyroid Neoplasm with Papillary like nuclear features (NIFTP), A time for change in Pakistan.

OBJECTIVE: To determine the cases of Noninvasive Follicular thyroid neoplasm with papillary like nuclear features (NIFTP) in Pakistani population retrospectively. Another objective was to determine their clinical and radiological outcomes with respect to local and systemic disease recurrence, reconfirming the benign course of this new nomenclature in Thyroid tumors by WHO in our population would encourage adopting the new conservative treatment approach in such patients. METHODS: This is a retrospective cohort study conducted at a tertiary care center in Karachi, Pakistan from 2007-2016. All follicular Variant papillary thyroid cancer (FVPTC) reported from a single institute had their histopathology slides reexamined for diagnosing NIFTP as per the new WHO criteria. These cases were then followed retrospectively from their diagnosis onset through their medical and electronic health record for any local or systemic disease recurrence. RESULTS: There were 199 cases of Papillary Thyroid cancer (PTC) which included 22 cases of FVPTC. Eleven cases fulfilled NIFTP criteria with tumor size ranging from 1.1cm to ≥ 5.5cm. All patients in the NIFTP group underwent total thyroidectomy. Nine patients (81.81%) received RAI131 therapy. Four (45%) patients had a median follow up of three to four years. There was no disease recurrence seen on both ultrasound and RAI scans of patients in the NIFTP group. Seven patients (87.5%) had normal surveillance thyroglobulin levels except one whereas three patients were lost to follow up. There was no disease recurrence seen both radiologically and biochemically in the NIFTP group. CONCLUSION: Our study favors the low risk nature of NIFTP with no disease recurrence in the cases studied and encourages de-escalation of treatment.

Maternal characteristics and outcomes affected by hypothyroidism during pregnancy (maternal hypothyroidism on pregnancy outcomes, MHPO-1).

BACKGROUND: Hypothyroidism in pregnancy is an arena of ongoing research, with international conflicts regarding screening, management, and outcomes. Various studies have described the outcomes depending on geographical and international diagnostic criteria. No study has been conducted in this regard from the region of Pakistan. Therefore, we aim to report the clinical features and maternal outcomes of hypothyroid pregnancies and compare the maternal outcomes between uncontrolled and controlled TSH levels in the preconception as well as the gestational period. METHODS: We conducted a cross-sectional retrospective study on 718 cases in the Aga Khan University Hospital after ethical approval. We collected information on pregnant females who have diagnosed hypothyroidism before conception or during their antenatal period. We noted the maternal characteristics and maternal comorbidities. Laboratory data were recorded for thyroid stimulating hormone levels before conception and during gestation. We recorded maternal outcomes as pregnancy loss (including miscarriage, stillbirth/intrauterine death, medical termination of pregnancy and ectopic pregnancy), gestational hypertension, pre-eclampsia, postpartum hemorrhage, placental abruption, and modalities of delivery. Data analysis was performed on Statistical Package for the Social Sciences version 20.0. RESULTS: Among 708 hypothyroid women 638 had live births. Postpartum hemorrhage was the most frequent maternal outcome (38.8%). The emergency cesarean section occurred in 23.4% of cases. We determined TSH levels in 53.2, 56.7, 61.7 and 66.6% of cases in preconception, 1st, 2nd, and 3rd trimester periods. A significant association existed between cesarean section and preconception thyrotropin levels > 2.5 mIU/L, whereas postpartum hemorrhage was significantly associated with thyrotropin levels > 2.5 mIU/L in the preconception and third trimester. CONCLUSION: Successful live births in our patients were complicated by maternal postpartum hemorrhage and a frequent number of emergency cesarean section.

IMPACT OF RAMADAN FASTING ON THYROID STATUS AND QUALITY OF LIFE IN PATIENTS WITH PRIMARY HYPOTHYROIDISM: A PROSPECTIVE COHORT STUDY FROM KARACHI, PAKISTAN.

OBJECTIVE: Ramadan is the ninth month in the lunar calendar, during which Muslims fast from predawn to sunset and major changes occur in their dietary, sleep, and physical activity patterns. Most patients with hypothyroidism are unable to comply with the proper timings of levothyroxine (LT4) administration. The objective of the study was to determine the change in thyroid-stimulating hormone (TSH) level and quality of life (QOL) before and after Ramadan in patients with primary hypothyroidism. METHODS: This prospective cohort study included adult patients on stable doses of LT4 who fasted for at least 20 days during the month of Ramadan in the Islamic year 1437 Hijri (June/July 2016). Baseline characteristics and TSH levels were recorded on all consenting patients within 6 weeks prior to Ramadan. Post-Ramadan TSH was tested within 1 to 2 weeks after Eid-ul-Fitr. RESULTS: During the study period, 64 patients with hypothyroidism were enrolled, of which 58 were female. The mean age of participants was 44.2 ± 13.2 years. Average daily dose of LT4 was 95.3 ± 35.4 µg. On average, patients fasted for 26.5 days and missed a dose of LT4 on 1.27 days. Mean TSH pre-Ramadan was 2.37 ± 1.35 mIU/L, and post-Ramadan, it was 4.69 ± 3.87 mIU/L. Mean difference between TSH pre- and post-Ramadan was 2.32 ± 3.80 mIU/L ( P<.001). However, the difference in TSH was not significantly different between those who were compliant with meals and LT4 interval versus those who were not (compliant, 2.04 mIU/L; noncompliant, 3.15 mIU/L; P = .30). Overall, an increase in QOL scores in the domains of physical health, psychological health, and social relationships was observed after Ramadan. CONCLUSION: We observed statistically significant changes in TSH concentrations after the month of Ramadan in hypothyroid patients who fasted. The change in TSH was not affected by timing of LT4 intake and interval from meal. ABBREVIATIONS: AKUH = Aga Khan University Hospital; LT4 = levothyroxine; QOL = quality of life; TSH = thyroid-stimulating hormone.

SODIUM AND WATER IMBALANCE AFTER SELLAR, SUPRASELLAR, AND PARASELLAR SURGERY.

OBJECTIVE: To report the frequency of sodium and water disturbances (SWDs) in patients undergoing sellar, suprasellar, and parasellar surgery (SSPS). METHODS: We conducted a cross-sectional, retrospective study on 115 patients in the Aga Khan University Hospital after ethical approval. Patients were 16 years old or older undergoing pituitary or sellar surgeries. We collected data on basic sociodemographic characteristics and clinical indication for surgery. We noted laboratory values for serum electrolytes, plasma and urine osmolality, urine sodium, and 24-hour fluid balance from the immediate postoperative day until discharge and follow-up. We recorded medical management plans. We also recorded diabetes insipidus (DI), syndrome of inappropriate antidiuretic hormone (SIADH), cerebral salt wasting (CSW), triphasic response, and hyponatremia, according to the diagnostic definitions. Finally, we performed data analysis using Statistical Package for the Social Sciences, version 19.0. RESULTS: Of 115 patients, there were 61.7% males, mean age 42.3 ± 13.86 years, 91.3% had pituitary adenoma (73.0% nonfunctioning), and 86.1% underwent transsphenoidal surgical approach. Transient DI occurred from days 1 to 6, peaking with 57.4% on day 2. Permanent DI and SIADH were rare. We did not note typical triphasic response or CSW in any of the patients. However, isolated hyponatremia occurred in 11%, and 20.9% had DI with hyponatremia. CONCLUSION: Transient DI is the most common postoperative SWD after SSPS. Hyponatremia occurred alone and following DI. This is the first study describing postoperative SWDs after different sellar surgeries in Pakistan. ABBREVIATIONS: ADH = antidiuretic hormone CSW = cerebral salt wasting DI = diabetes insipidus SIADH = syndrome of inappropriate antidiuretic hormone SSPS = sellar, suprasellar, and parasellar surgery SWD = sodium and water disturbance.

Diabetic ketoacidosis characteristics and differences In type 1 versus type 2 diabetes patients.

BACKGROUND: Diabetes is undoubtedly one of the most challenging health problems of the 21st century. It is well known that diabetes once develop can lead to several complications. Diabetic ketoacidosis (DKA) is one of the life-threatening complications of diabetes. This study was designed to determine the frequency of DKA in diabetes patients and find out the clinical and biochemical determinants of DKA. METHODS: This descriptive study was conducted at Aga Khan University Hospital (AKUH) Karachi, Pakistan from January 2010 to February 2016. All known or newly diagnosed diabetic patients of >16 years of age irrespective of gender and type of diabetes were included. Information regarding patient's demographics, presenting symptoms, precipitating causes of DKA, biochemical profiles and outcome at the time of discharge was collected. RESULTS: Majority (54.7%) had moderate and 12.4% had severe DKA at presentation. Previous history of DKA was found higher in type 1 diabetes patients (T1DM) (14%) as compare to (4%) type 2 diabetes patients (T2DM) (p<0.05). DKA severity was observed more (12%) in newly diagnosed (T1DM) (p<0.05). Comorbidities were found more (81%) in (T2DM) (p<0.05) Mortality was also observed higher in Type 2 diabetes patients (p<0.05). CONCLUSIONS: Majority of the diabetics had moderate to severe DKA at presentation. Mortality and morbidity related with DKA was found considerably higher among patients with T2DM while infection, myocardial infarction and stroke found as triggering factors in these patients.

Glucose monitoring in pregnancy complicated by diabetes.

Diabetes in pregnancy is associated with adverse maternal and neonatal outcomes. Due to variations in insulin resistance throughout pregnancy there is a continuous need to implement Medical Nutrition Therapy (MNT), exercise and pharmacological treatments which have to be escalated. Self-monitoring of blood glucose (SMBG) is integral to the management of diabetes in pregnancy. Proper implementation of SMBG in pregnant women with diabetes requires patient education and understanding of its applications and limitations. Real-time results enable individuals to make informed daily self-care decisions regarding diet, exercise, and insulin. Retrospective analysis of SMBG data enables clinicians to develop individualized care plans, informing decisions related to insulin initiation and adjustment and the possible needs for interventions or hospitalization to improve inadequate self-monitoring.

Comparison of Factors Influencing Gestational Outcomes in Healthy Versus Hypothyroid Women from Karachi, Pakistan.

BACKGROUND: Gestational outcomes are known to be negatively correlated with hypothyroidism. This study was designed to compare the maternal factors affecting gestational outcomes in women with and without hypothyroidism. METHODS: This retrospective analysis was carried out in a tertiary hospital in Karachi, Pakistan, between 2008 and 2016. A standardized form was used to collect information on the age of the mother, gestational duration at the prenatal appointment, gestational diabetes mellitus (GDM), hypertension, and past records of miscarriages in hypothyroid and healthy pregnant women. Gestational outcomes were recorded as live birth or pregnancy loss. Statistical analysis was performed to examine overt versus sub-clinical hypothyroidism and among those diagnosed before versus during gestation. RESULTS: A collective of 708 women were enlisted in the hypothyroid pregnant group and 759 were recruited in healthy controls. Pregnancy loss was 9.9% (n=70) in hypothyroid women, whereas it was 14.3% (n=108) in the control group. The age of the mother, gestational duration at the prenatal appointment, and past records of miscarriages were discovered to be related to a higher chance of pregnancy loss in a multivariable analysis, but GDM (OR 0.04, CI 0.06-0.32, P=0.002) and hypothyroidism (OR 0.62, CI 0.43-0.89, P=0.01) exhibited a protective effect. CONCLUSION: This study found the age of the mother, gestational duration at a prenatal appointment, and past records of miscarriages to be associated with negative outcomes in hypothyroidism. These factors remained significant in overt as well as subclinical hypothyroid women.

Global Warming and Endocrinology: The Hyderabad Declaration of the South Asian Federation of Endocrine Societies.

Global warming and endocrine disorders are intertwined issues posing significant challenges. Greenhouse gases emanating from human activities drive global warming, leading to temperature rise and altered weather patterns. South Asia has experienced a noticeable temperature surge over the past century. The sizable population residing in the region heightens the susceptibility to the impact of global warming. In addition to affecting agriculture, water resources, and livelihood, environmental changes interfere with endocrine functioning. Resulting lifestyle changes increase the risk of metabolic and endocrine disorders. Individuals with diabetes face heightened vulnerability to extreme weather due to impaired thermoregulation. A high ambient temperature predisposes to heat-related illnesses, infertility, and nephropathy. Additionally, essential endocrine drugs and medical devices are susceptible to temperature fluctuations. The South Asian Federation of Endocrine Societies (SAFES) calls for collaboration among stakeholders to combat climate change and promote healthy living. Comprehensive approaches, including the establishment of sustainable food systems, promotion of physical activity, and raising awareness about environmental impacts, are imperative. SAFES recommends strategies such as prioritizing plant-based diets, reducing meat consumption, optimizing medical device usage, and enhancing accessibility to endocrine care. Raising awareness and educating caregivers and people living with diabetes on necessary precautions during extreme weather conditions are paramount. The heat sensitivity of insulin, blood glucose monitoring devices, and insulin pumps necessitates proper storage and consideration of environmental conditions for optimal efficacy. The inter-connectedness of global warming and endocrine disorders underscores the necessity of international collaboration guided by national endocrine societies. SAFES urges all stakeholders to actively implement sustainable practices to improve endocrine health in the face of climate change.

Safety of sodium-glucose cotransporter 2 inhibitors (SGLT2i) during the month of Ramadan in patients with type 2 diabetes mellitus in Pakistani population-an observational study from a tertiary care center in Karachi.

BACKGROUND AND AIMS: Primary aim was to assess the safety of SGLT2-i in patients with Type 2 Diabetes Mellitus (T2D) in a real-life scenario during Ramadan by finding the frequency and severity of hypoglycemic/hyperglycemic events, dehydration, and Diabetic ketoacidosis (DKA). Secondary aim was to assess changes in glycated hemoglobin (HbA1c), weight and creatinine levels. METHODS: This prospective, observational, controlled cohort study was conducted at Aga Khan University Hospital, Karachi, Pakistan from March 15 to June 30, 2021. Participants were over 21 years of age, on stable doses of SGLT2-I, which was started at least 2 months before Ramadan. Endpoint assessments were done 1 month before and within 6 weeks after Ramadan. RESULTS: Of 102 participants enrolled, 82 completed the study. Most (52%) were males, with mean age 52.2 ± 9.5 years and average duration of T2D 11.2 ± 6.5 years. 63% were on Empagliflozin (mean dose; 14.8 ± 7.2 mg/day) whereas 37% were on Dapagliflozin (mean dose; 8.2 ± 2.7 mg/day). Six (7.3%) documented symptoms of hypoglycemia. However, no episode of severe hypoglycemia, hyperglycemia, dehydration, DKA, hospitalization or discontinuation of SGLT2i was reported. HbA1c changes were (7.7 ± 1.2% from 7.9 ± 2.3%, p 0.34), weight (78.4 ± 12.9 kgs from 78.9 ± 13.3, p 0.23) and eGFR (87.8 ± 27.9 from 94.3 ± 37.6, p < 0.001). The reasons of study participants drop outs were: six did not keep any fasts; four discontinued study participation for personal reasons; three were out of city and missed post Ramadan follow-up, two protocol violation and five could not be contacted for post-Ramadan follow up during the third wave of COVID-19. CONCLUSION: Results showed the safety of SGLT2i agents during Ramadan in the Pakistani population recommending it as a treatment option in adults with T2D, without any additional adverse events.

Standardized Tapering off Subcutaneous Immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy.

BACKGROUND: Attempting discontinuation of treatment in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) is recommended. However, there is no evidence based regimen for tapering off subcutaneous immunoglobulin (SCIG). This trial investigated stepwise tapering off SCIG to detect remission and the lowest effective dosage. During tapering off, frequent vs less frequent clinical evaluation was compared. METHODS: Patients with CIDP receiving a stable SCIG dosage followed a standardized tapering off regimen: 90%, 75%, 50%, 25% and 0% of the initial dose every 12th week, pending no deterioration occurred. In case of relapse during tapering off, the lowest effective dose was identified. Treatment with SCIG was registered for two years after participation. Disability score and grip strength were primary parameters. Participants were randomized to clinical evaluation every 6th week (frequent) or 12th week (less frequent). RESULTS: Fifty-five patients were included of which thirty-five relapsed. Twenty patients (36%) were able to discontinue treatment without relapse. In relapsing patients, median dosage could be reduced by 10% (range, 0-75). After two years, 18 of 20 patients were still in remission without treatment. Frequent clinical evaluation did not detect deterioration more frequently than less frequent evaluation; RR 0.5 (95% CI, 0.2-1.2) (p = 0.17). CONCLUSION: In stable CIDP patients, SCIG could be completely tapered off in 36% of the patients and only in 10% of these patients relapse occurred during the following two years. More frequent evaluation was not superior to detect deterioration.

GRADE-ADOLOPMENT of clinical practice guideline for postmenopausal osteoporosis management-a Pakistani context.

Due to its high prevalence, we aimed to create postmenopausal osteoporosis clinical practice guideline via GRADE-ADOLOPMENT for Pakistan. We recommend a higher dose (2000-4000 IU) of vitamin D for osteoporotic patients who are old, have malabsorption, or are obese. The guideline will help standardize care provision and improve health care outcomes for osteoporosis. PURPOSE: Postmenopausal osteoporosis affects one in every five postmenopausal women in Pakistan. An evidence-based clinical practice guideline (CPG) is needed to standardize care provision to optimize health outcomes. Hence, we aimed to develop CPG for the management of postmenopausal osteoporosis in Pakistan. METHODS: The GRADE-ADOLOPMENT process was used to adopt (as is or with minor changes), exclude (omit), or adapt (modify based on local context) recommendations to the source guideline (SG)-clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis-2020 update from American Association of Clinical Endocrinology (AACE). RESULTS: The SG was "adoloped" to cater to the local context. The SG consisted of 51 recommendations. Forty-five recommendations were adopted as is. Due to unavailability of drugs, 4 recommendations were adopted with minor changes, and one was excluded, while one recommendation was adopted with the inclusion of use of a surrogate FRAX tool specific for Pakistan. One recommendation regarding vitamin D dosage was adapted to recommend a dose of 2000-4000 IU of vitamin D in patients with obesity, malabsorption, and old age. CONCLUSION: The developed Pakistani postmenopausal osteoporosis guideline consists of 50 recommendations. The guideline created recommends a higher dose (2000-4000 IU) of vitamin D for patients who are old, have malabsorption, or are obese, which is an adaptation from the SG by the AACE. This higher dose is justified as lower doses prove to be suboptimal in these groups and should be complemented with baseline vitamin D and calcium levels.